Title
The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila
UMMS Affiliation
Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Publication Date
2016-09-01
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Abstract
A major function of ubiquitylation is to deliver target proteins to the proteasome for degradation. In the apoptotic pathway in Drosophila, the inhibitor of apoptosis protein 1 (Diap1) regulates the activity of the initiator caspase Dronc (death regulator Nedd2-like caspase; caspase-9 ortholog) by ubiquitylation, supposedly targeting Dronc for degradation by the proteasome. Using a genetic approach, we show that Dronc protein fails to accumulate in epithelial cells with impaired proteasome function suggesting that it is not degraded by the proteasome, contrary to the expectation. Similarly, decreased autophagy, an alternative catabolic pathway, does not result in increased Dronc protein levels. However, combined impairment of the proteasome and autophagy triggers accumulation of Dronc protein levels suggesting that autophagy compensates for the loss of the proteasome with respect to Dronc turnover. Consistently, we show that loss of the proteasome enhances endogenous autophagy in epithelial cells. We propose that enhanced autophagy degrades Dronc if proteasome function is impaired.
DOI of Published Version
10.1038/cdd.2016.40
Source
Cell Death Differ. 2016 Sep 1;23(9):1555-64. doi: 10.1038/cdd.2016.40. Epub 2016 Apr 22. Link to article on publisher's site
Journal/Book/Conference Title
Cell death and differentiation
Related Resources
PubMed ID
27104928
Repository Citation
Lee, T. V.; Kamber Kaya, H. E.; Simin, Rachel T.; Baehrecke, Eric H.; and Bergmann, Andreas, "The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila" (2016). Molecular, Cell and Cancer Biology Publications. 60.
https://escholarship.umassmed.edu/mccb_pubs/60